Clinical Trials Register

Summary
EudraCT Number:	2006-006519-60
Sponsor's Protocol Code Number:	D5892C00014
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2007-03-15
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Germany - BfArM

A.2

EudraCT number

2006-006519-60

A.3

Full title of the trial

A multi-centre, randomised, double-blind, cross-over design study to evaluate efficacy on exercise tolerance of budesonide/formoterol (Symbicort®Turbuhaler®) 320/9 μg one inhalation twice daily compared with placebo and formoterol (Oxis®) Turbuhaler 9 μg one inhalation twice daily in patients with severe chronic obstructive pulmonary disease (COPD).

A.3.2

Name or abbreviated title of the trial where available

CODEX

A.4.1

Sponsor's protocol code number

D5892C00014

A.5.1

ISRCTN (International Standard Randomised Controlled Trial) Number

N/A

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	AstraZeneca AB
B.1.3.4	Country	Sweden
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Symbicort Turbuhaler 320/9 microgram/inhalation
D.2.1.1.2	Name of the Marketing Authorisation holder	AstraZeneca AB
D.2.1.2	Country which granted the Marketing Authorisation	Sweden
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Inhalation powder
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Inhalation use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	BUDESONIDE
D.3.9.1	CAS number	51333223
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	320
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	FORMOTEROL FUMARATE
D.3.9.1	CAS number	43229807
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	9
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Information not present in EudraCT
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Information not present in EudraCT
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Oxis Turbuhaler 9 microgram/inhalation
D.2.1.1.2	Name of the Marketing Authorisation holder	AstraZeneca AB
D.2.1.2	Country which granted the Marketing Authorisation	Sweden
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Inhalation powder
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Inhalation use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	FORMOTEROL FUMARATE
D.3.9.1	CAS number	43229807
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	9
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Information not present in EudraCT
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Information not present in EudraCT
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Inhalation powder
D.8.4	Route of administration of the placebo	Inhalation use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Inhalation powder
D.8.4	Route of administration of the placebo	Inhalation use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Severe Chronic Obstructive Pulmonary Disease (COPD)

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	9.1
E.1.2	Level	LLT
E.1.2	Classification code	10010952
E.1.2	Term	COPD

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective of this study is to compare the efficacy on exercise tolerance of
Symbicort Turbuhaler 320/9 microgram twice daily compared to placebo and Oxis Turbuhaler 9 microgram twice daily in patients with severe COPD by evaluation of the Exercise Endurance Time (EET) measured at 75% of Wmax with cycle ergometry 1 hour post-dose at visits 5, 7 and 9 (end of each treatment period) as the primary outcome variable.

E.2.2

Secondary objectives of the trial

The secondary objective of the study is to evaluate safety by assessing the nature and incidence of AEs.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Provision of informed consent prior to conducting any study-related procedure
2. Out-patient, man or woman ≥40 years of age
3. A clinical diagnosis of COPD, and symptoms for more than 2 years prior to visit 2
4. A current or previous smoker with a smoking history equivalent to 10 or more
pack years (1 pack year = 20 cigarettes smoked per day for one year)
5. A history of at least one COPD exacerbation requiring a course of oral steroids
and/or antibiotics within 1-12 months before visit 2
6. FEV1≤50% of predicted normal value (pre-bronchodilator)
7. FEV1/VC<70% (pre-bronchodilator)
8. FRC≥120% of predicted normal value (pre-bronchdilator)
9. Wmax at least 20 watts from the incremental exercise test at visit 2
10. Ability to safely perform the maximal exercise test on cycle without medical
contraindications
11. Documented use of short-acting inhaled bronchodilator (β2-agonists or
anticholinergics) as reliever medication
12. Able to read and write and use the electronic devices (eDiary and ePEF)

E.4

Principal exclusion criteria

1. A history of asthma.
2. A history of seasonal allergic rhinitis before 40 years of age
3. Exacerbation of COPD during run-in or within 4 weeks (end of exacerbation)
prior to visit 2, requiring hospitalisation, a course of oral and/or inhaled steroids
and/or antibiotics
4. Significant or unstable ischemic heart disease, arrhythmia, cardiomyopathy, heart
failure, uncontrolled hypertension as defined by the investigator, or any other
relevant cardiovascular disorder as judged by the investigator
5. Regular oxygen therapy
6. Any current respiratory tract disorder other than COPD, which is considered by
the investigator to be clinically significant
7. Any significant disease or disorder which, in the opinion of the investigator, may
either put the patient at risk because of participation in the study, or influence the
results of the study, or the patient’s ability to participate in the study
8. Signs and symptoms of peripheral arterial occlusion
9. SaO2≤90% at rest
10. Any abnormality in ECG that could put patient at risk while performing exercise
testing, as judged by the investigator
11. Patient taking non-cardioselective β-blocking agents
12. Use of inhaled corticosteroids within 2 weeks prior to visit 2 and during run-in.
13. Use of oral/parenteral corticosteriods within 4 weeks prior to visit 2 and during run-in.
14. Pregnancy, breast-feeding or planned pregnancy during the study. Fertile women
not using acceptable contraceptive measures. Acceptable contraceptive methods
are methods of birth control which result in a low failure rate (ie, less than 1 %
per year) when used constantly and correctly such as implants, combined oral
contraceptives, some intrauterine devices, sexual abstinence or vasectomised
partner
15. Known or suspected hypersensitivity to study therapy or excipients of the
investigational products
16. Scheduled in-patient hospitalisation during the course of the study
17. Patients who have participated in a clinical study evaluating an investigational
product in the last 4 weeks prior to enrolment, or during this study, or who have been previously
allocated a randomisation code in this study
18. Patients with a history of chronic alcohol or drug abuse or any condition associated with poor compliance
19. Patients participating in or scheduled for an intensive COPD rehabilitation program
20. Any clinically relevant abnormal findings in physical examination and vital signs,
which in the opinion of the investigator, may put the patient at risk because of
his/her participation in the study
21. Planned donation of blood during the study
22. Involvement in the planning and conduct of the study (applies to both AstraZeneca staff or staff at the study site)

E.5 End points

E.5.1

Primary end point(s)

The Primary efficacy variable will be:
- Exercise Endurance Time (EET) performed at 75% of Peak Work Capacity
(Wmax) with cycle ergometry (1 hour post dose)

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

E.8.1.6

Cross over

Yes

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

The end of the study is defined as date of database lock, which is the time point after which no patient will be exposed to study related activities.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects
F.1 Age Range
F.1.1	Trial has subjects under 18	No
F.1.1.1	In Utero	Information not present in EudraCT
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	Information not present in EudraCT
F.1.1.3	Newborns (0-27 days)	Information not present in EudraCT
F.1.1.4	Infants and toddlers (28 days-23 months)	Information not present in EudraCT
F.1.1.5	Children (2-11years)	Information not present in EudraCT
F.1.1.6	Adolescents (12-17 years)	Information not present in EudraCT
F.1.2	Adults (18-64 years)	Yes
F.1.3	Elderly (>=65 years)	Yes
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	Yes
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	Yes
F.3.3.1	Women of childbearing potential not using contraception	No
F.3.3.2	Women of child-bearing potential using contraception	Yes
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	90
F.4.2	For a multinational trial
F.4.2.1	In the EEA	90
F.4.2.2	In the whole clinical trial	100

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2007-05-22

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2007-05-16

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2008-08-22

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